Jonathan W. Riess, MD, MS
A Danish population-based cohort study by Ehrenstein and colleagues involved 21,282 patients with non–small-cell lung cancer (NSCLC), 8758 of whom received a diagnosis at stage I-IIIA. Of those, 4071 (46%) were tested for epidermal growth factor receptor ( EGFR) mutations at diagnosis. Median overall survival (OS) was 5.7 years among patients with EGFR mutation–positive status (n = 361) and 4.4 years among patients with EGFR mutation–negative status (n = 3710). EGFR mutation–positive status was associated with lower all-cause mortality in all subgroups. This is not surprising, because EGFR-mutated lung cancers are associated with never or light smoking history and the patients tend to be younger and have fewer medical comorbidities. Nevertheless, the lower risk for all-cause mortality was consistent across all subgroups (stage at diagnosis, age, sex, comorbidity, and surgery receipt), with hazard ratios (HR) ranging from 0.48 to 0.83. In addition, targeted therapies, such as osimertinib, improved OS and progression-free survival (PFS) in the metastatic setting as first-line treatment. Now that the ADAURA study has demonstrated a substantial disease-free survival benefit with osimertinib in the adjuvant setting in early-stage EGFR-mutated NSCLC (with final OS results still to come) it will be interesting to see whether this magnitude of difference in OS grows over time.
Wang and colleagues conducted a large meta-analysis of 10 retrospective studies and one prospective study including a total of 5892 patients with NSCLC who were receiving programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors with the concomitant use of gastric acid suppressants (GAS). Use of PD-1/PD-L1 inhibitors with vs without GAS worsened PFS by 32% (HR 1.32; P < .001) and OS by 36% (HR 1.36; P < .001). The GAS in these studies were predominantly proton-pump inhibitors (PPI). There is still much to learn about medications that may influence outcomes to immune checkpoint blockade, such as steroids, antibiotics, GAS, and others. We are also learning that the microbiome probably plays an important role in contributing to activity of PD-1/PDL-1 antibodies and PPI may modify the microbiome. More research is needed, but it is reasonable to try and switch patients receiving PD-1/PDL-1 inhibitors from PPI to other GAS, if clinically appropriate.
Nazha and colleagues performed a SEER-Medicare database analysis evaluating 367,750 patients with lung cancer. A total of 11,061 patients had an initial prostate cancer diagnosis and subsequent lung cancer diagnosis, 3017 had an initial lung cancer diagnosis and subsequent prostate cancer diagnosis, and the remaining patients had an isolated lung cancer diagnosis. Patients who received androgen deprivation therapy (ADT) for a previously diagnosed prostate cancer showed improved survival after lung cancer diagnosis (adjusted HR for death 0.88; P = .02) and a shorter latency period to the diagnosis of lung cancer (40 vs 47 months; P < .001) compared with those who did not receive ADT. This finding applied mainly to White patients and may not apply to Black patients because there was an underrepresentation of Black patients in the study. The association of ADT for prostate cancer improving clinical outcomes in patients subsequently diagnosed with lung cancer is intriguing. There is known crosstalk between receptor kinase signaling and androgen receptor signaling that may biologically explain the findings in this study. This theoretically could apply more to certain molecular subtypes of lung cancer, such as EGFR-mutated lung cancer. However, further studies are needed to confirm this because confounding factors and immortal time bias (where patients receiving ADT may be more likely to have more frequent interactions in the healthcare system and thus receive an earlier lung cancer diagnosis) may in part explain the findings in this retrospective analysis. More research is needed to determine whether patients with prostate cancer receiving ADT had improved survival compared with those who did not receive ADT.